Mycophenolic acid (MPA, also known as 6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoic acid, 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid, C17H20O6, CAS 24280-93-1) is a compound with various advantageous properties. Next to antibiotic activity, MPA also displays antifungal, antiviral and antitumor properties and the compound has been used in the treatment of psoriasis and recently as immunosuppressant. The 2-morpholinoethyl ester of MPA, also known as mycophenolate mofetil (MPM, C23H31NO7, CAS 128794-94-5), is a prodrug of MPA and has similar advantageous properties. The chemical structure of MPM is:

MPM can be prepared by esterification of MPA with 2-morpholinoethanol. In U.S. Pat. No. 4,753,935 an acid halide condensation route has been described. This is a two-step process requiring toxic reagents for forming the halide of MPA and/or of 2-morpholinoethanol. In EP 649,422 B1, an improved route was disclosed concerning refluxing MPA with 2-morpholinoethanol in an inert organic solvent capable of azeotropic removal of water, without the use of additional reagents. One of the major problems associated with the synthesis of MPM is the formation of unwanted impurities. One of those impurities is Impurity B (C29H42N2O9) which has the following chemical structure:

The origin of Impurity B is believed to reside in the production process leading to MPA, where a hydroxylated derivative of MPA (MPA-OH, C17H21O7) is formed which is then converted to Impurity B during esterification with 2-morpholinoethanol, however also other hypotheses are feasible. The chemical structure of MPA-OH is:

Regardless of the origin of Impurity B, synthetic and/or downstream processing methods towards the preparation of MPM with acceptable levels of Impurity B are highly desirable. According to the European Pharmacopoeia not more than 0.2% Impurity B may be present in MPM. Known approaches towards lowering the amount of Impurity B are well-known techniques such as recrystallization and/or chromatographic purification as for instance suggested in U.S. Pat. No. 5,247,083. However, such approaches result in significant losses of the desired product MPM and both are cumbersome and expensive, the last issue being particularly true for chromatographic purification. Hence, there is a need for an efficient and cheap method for lowering the amount of Impurity B in MPM.